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BackgroundLupus low disease activity state (LLDAS) attainment has been reported to be associated with reduced damage accrual, flare, and mortality, as well as improved quality of life, in cohorts of SLE patients with established disease. Whether these associations are present in recent-onset disease is less well known.ObjectivesTo evaluate the associations of LLDAS attainment with outcomes in patients with recent onset SLE.MethodsData from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected prospectively between 2013 and 2020 using standard templates. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golder et al., 2019 [1]. An inception cohort was defined based on duration since SLE diagnosisResultsThe study cohort included 4,106 patients of whom 680 (16%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the non-inception cohort, inception cohort patients were significantly younger, had higher disease activity (SLEDAI-2K and physician global assessment), used more glucocorticoids and immunosuppressants but had less organ damage at enrolment and only 88 (13.6%) patients accrued damage during a median 2.2 years follow-up (Table 1).Table 1.Non-inception cohortInception cohortp-valuen=3426n=680Age at enrolment (years), median [IQR]40 [31, 51]33 [25, 44]Age at diagnosis (years), median [IQR]28 [21, 38]33 [25, 43]SLE duration at enrolment (years), median [IQR]10 [5, 16]1 [0, 1]Study duration (years), median [IQR]2.5 [1.0, 5.4]2.2 [0.9, 3.7]Females, n (%)3155 (92.1%)623 (91.6%)0.68Asian ethnicity, n (%)3037 (89.1%)595 (88.1%)0.49Prednisolone (PNL) use - ever, n (%)2865 (83.6%)620 (91.2%)Time adjusted mean (TAM)-PNL, median [IQR]5.0 [2.2, 8.6]6.2 [3.2, 10.3]Cumulative PNL (g), median [IQR]3.4 [0.5, 9.7]3.8 [1.1, 8.5]0.26Anti-Malarial use - ever, n (%)2669 (77.9%)569 (83.7%)Immunosupressant use -ever, n (%)2367 (69.1%)521 (76.6%)AMS (TAM-SLEDAI-2K), median [IQR]2.8 [1.2, 4.6]3.1 [1.6, 5.0]0.002TAM-PGA, median [IQR]0.4 [0.2, 0.7]0.4 [0.3, 0.8]Mild/moderate/severe flare ever, n (%)1789 (52.2%)391 (57.5%)0.012Organ damage accrual, n (%)629 (20.8%)88 (13.6%)LLDAS at baseline, n (%)1730 (50.5%)195 (28.7%)LLDAS-ever (at least once), n (%)2637 (78.2%)492 (73.9%)0.014≥50% time in LLDAS (LLDAS-5), n (%)1612 (50.6%)256 (41.1%)Significantly fewer inception cohort patients were in LLDAS at enrolment than the non-inception cohort (29% vs. 51%, pConclusionLLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed, due to low rates of damage accrual in the first years after SLE diagnosis.References[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.AcknowledgementsWe thank all patients participating in the Asia Pacific Lupus Collaboration (APLC) cohort, and all data collectors for their ongoing support for APLC research activities.The APLC has received unrestricted project grants from AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, and UCB to support data collection contributing to this work.Disclosure of InterestsVera Golder: None declared, Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra& Zeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, GSK, Astra and Zeneca, Sanofi, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Yes. Clinical trials and/or research grants from Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche,Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca,Astellas, Gilead, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson, Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Yes. Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., Masayoshi Harigai Speakers bureau: MH has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: MH is a consultant for AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: MH has received research grants from AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, BMDB Basnayake: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Advisory Board member for Pfizer, Eli-Lilly, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K, Sang-Cheol Bae: None declared, Sean O’Neill Paid instructor for: Advisory board member for GSK, Fiona Goldblatt: None declared, Shereen Oon: None declared, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis – co-chair for NSW and steering committee member for ARISE meeting Feb 2021Janssen Pharmaceuticals – advisory board, Grant/research support from: Novartis, Employee of: Eli Lilly, Kristine Ng Speakers bureau: speaker fees and advisory board (Abbvie, Novartis, Janssen), Annie Law: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, C.S. Lau Shareholder of: Pfizer, Sanofi and Janssen, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Consultant of: AH is on the advisory board for Abbvie and GSK, Grant/research support from: AH has received research support from AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen

Background:The recent prospectively validated definition of the lupus low disease activity state (LLDAS) allows characterisation of patients not achieving a treatment goal, providing impetus for an analysis of unmet needs in SLE using formal definitions. Other recently described definitions of high disease burden include disease activity over time, high disease activity status (HDAS) episodes, and the combination of high disease activity, serological activity and glucocorticoid (GC) use (HDAS+SA+GC).Objectives:To determine the prevalence of formal categories of unmet need, and the association of these with adverse outcomes, in SLE.Methods:Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected between 2013 and 19 using standard templates. Unmet need was defined as (i) patients never attaining LLDAS defined as in Golder et al., 2019 [1], (ii) having persistently active disease (time adjusted mean SLEDAI-2K (AMS) > 4), (iii) ever exhibiting high disease activity status (HDAS; SLEDAI-2K ≥10[2]), or (iv) ever exhibiting all of SLEDAI≥10, serological activity, and glucocorticoid use (HDAS+SA+GC)[3]. Health-related quality of life (HRQoL) was assessed using SF36 (v2) surveys and damage accrual using SLE Damage Index (SDI).Results:3,384 SLE patients were followed for 30,313 visits over median [IQR] 2.4 [0.4, 4.3] years. 53% of all visits were not in LLDAS; 813 patients (24%) never achieved LLDAS during observation. Median AMS was 3.0 [1.4, 4.9] and 34% of patients had AMS > 4 throughout the study. 25% of patients had at least one episode of HDAS, representing 8% of visits. 702 patients (21%) had at least one episode of HDAS+SA+GC, representing 8% of visits. Each of never-LLDAS, AMS>4, ever-HDAS, and ever-HDAS+SA+GC were associated with significantly greater number of physician visits, higher mean glucocorticoid dose, lower HRQoL and higher mortality. 31%, 58% and 83% of never-LLDAS, AMS>4, and ever-HDAS patients respectively were also HDAS+SA+GC on at least one occasion.Conclusion:Data from a multinational longitudinal SLE cohort indicate that unmet need, defined by LLDAS-never, AMS>4, HDAS, or HDAS+SA+GC, is prevalent in SLE, and that these definitions are associated with poor outcomes.References:[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[2]Koelmeyer, R., et al., High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7(1).[3]van Vollenhoven, R.F., et al., Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Annals of the Rheumatic Diseases, 2012. 71(8): p. 1343-1349.Acknowledgements:The APLC acknowledges all the Data Collectors and Patients for their valuable contributions to research.Disclosure of Interests:Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Consultant of: Abbvie and GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Vera Golder: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche, Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca, Astellas, Gilead, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Aisha Lateef: None declared, Jiacai Cho: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Chak Sing Lau Shareholder of: Pfizer, Sanofi, and Janssen, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson., Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., masayoshi harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie, Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K., BMDB Basnayake: None declared, Fiona Goldblatt: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Pfizer, Eli-Lilly, Kristine Ng Speakers bureau: Abbvie, Novartis, Janssen, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O’Neill Consultant of: GSK, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis, Janssen, Grant/research support from: Novartis, Sunil Kumar: None declared, Nicola Tugnet: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen.